ABSTRACT: 

Background & Aims: Phantom limb pain (PLP) is a frequent complication following limb amputation and can be characterized by cold or electrical sensations, burning, throbbing, stabbing, or cramping features.  Currently, an optimal pharmacological treatment regimen for chronic PLP remains unclear.  Further investigation for safe and efficacious therapies is warranted given how debilitating phantom pain may be on a person’s quality of life and well-being.  While the pathophysiology of PLP is poorly understood, proposed mechanisms for the development of PLP include the development of neuromas (unorganized groups of hyperexcitable afferent peripheral nerve fibers) and central sensitization of the spinal cord (expansion of the neural receptive field and subsequent increase in N-methyl-D-aspartate (NMDA) and glutamate receptor activity).  It has been proposed that ketamine, a NMDA and glutamate receptor antagonist, may theoretically target areas of increased NMDA and glutamate receptor activity, making it an ideal drug for prospective research in this field.  However, the feasibility of intravenous or oral ketamine use in practice and in translational research has historically been and remains problematic given its notorious psychogenic side effect profile and notorious potential for abuse.  In efforts to ameliorate these obstacles and maximize the potential benefits that may be utilized from ketamine, this study investigates and discusses both the current therapies and the potential of topical ketamine for patients with post-amputation phantom pain based on a review of current literature.  

Methods: A Pubmed search was performed to review previously published pharmacological and clinical research regarding the use of systemic and topical ketamine for various kinds of neuropathic pain including phantom limb pain.  Thirteen clinical studies were identified and included in the final review analysis. 

Findings:  There was sufficient evidence from previous studies investigating systemic and topical ketamine for PLP and other kinds of neuropathic pain to conclude that ketamine, whether given topically or in low doses orally or intravenously, can achieve significant analgesic effects without producing concerning psychogenic side effects.  In the clinical studies investigating the use of topical ketamine, side effects were minimal with no serious adverse events reported.  

Conclusions:  Overall, it was concluded that the current evidence supporting topical ketamine use for neuropathic pain relief is significant enough to warrant prospective research investigating its potential as a long-term treatment option for patients experiencing post-amputation PLP.  In efforts to reduce systemic adverse effects, to decrease the dosing requirements through bypassing first pass hepatic metabolism, and to provide long-term relief directly to the localized area of pain, topical ketamine should be considered as an option for PLP patients.